Clinical geneticist and biotech entrepreneur Hugh Rienhoff is a longtime user of Ingenuity applications, trusting these tools for studies ranging from clinical trials of a new drug to understanding the genetic mysteries of his own daughter.

Rienhoff, trained as a hematologist and clinical geneticist, branched out to try venture capital investing in the 1990s but preferred a role mixing scientist and entrepreneur. In 2007, he founded and served as CEO of FerroKin BioSciences, a company focused on therapeutics for iron-overload treatment, which was sold to Shire plc in 2012. Today, he is founder and CEO of Imago BioSciences, a biotech company developing therapeutics for genetic disorders.

At FerroKin BioSciences, Rienhoff worked to solve a serious medical challenge: some patients with hereditary anemias like sickle cell disease need regular transfusions to survive, but those very transfusions invariably result in iron overload, which can be fatal. His goal was to find an effective iron chelator without major side effects that could help these patients enjoy longer, more normal lives.

In one study, Rienhoff and his colleagues assessed 45 patients with thalassemia major, a heritable anemia in which too little hemoglobin is made. While patients were being studied on the new iron chelator, their exomes were sequenced with the goal of identifying genetic variants associated with specific clinical phenotypes such as transfusion requirements, pharmacokinetics, and pharmacodynamic responses. The data were analyzed in the Ingenuity Variant Analysis suite of tools. “I used the Ingenuity system extensively for that study,” Rienhoff says. “It was really the only analytical tool I could find to make sense of that data.” That work was absorbed by Shire when it acquired FerroKin, along with a promising drug currently in late phase 2 clinical trials.

Despite his history as a biotech pioneer, Rienhoff may be best recognized as the founder of MyDaughtersDNA.org and his quest to identify the genetic mutation underlying the clinically undescribed syndrome with which his daughter Beatrice was born in 2003. Nine years later, Rienhoff and a team of clinicians and scientists reported a never-before-seen variant in TGF-β3 that appears to explain the signs and symptoms of Beatrice’s syndrome. After years of hunting through stretches of Beatrice’s DNA, Rienhoff found the mutation — and loaded his exomes into Ingenuity Variant Analysis to confirm, and eventually publish, the results.

During that nine-year odyssey, Rienhoff brought Bea’s case to the attention of doctor after doctor, scientist after scientist, hunting down every lead that arose. Certain symptoms fit with Marfan syndrome, but it wasn’t Marfan. Other symptoms matched Loeys Dietz syndrome, but it wasn’t that. While these syndromes did not provide a diagnosis, the overlap did help to narrow the search for which pathways might be affected and hence which genes might be at the root of Bea’s condition.

Eventually, Illumina performed sequencing for not just Bea’s exome but also those of her two older siblings and both of her parents for comparative purposes. The sequencing company conducted analysis of the data, finding a likely candidate in the TGF-β signaling pathway — the same pathway implicated in Marfan and Loeys Dietz syndromes.

Based on his prior experience with the Ingenuity platform, Rienhoff says, “It seemed natural to load the exomes in and analyze them the Ingenuity way.” Ingenuity Variant Analysis identified three mutations that were likely deleterious, one of which was the same TGF-β3 variant that Illumina’s filtering had turned up. That mutation was reported in a 2013 publication in the American Journal of Medical Genetics and data were made publicly available through the Variant Analysis Publish feature.

This blog post was excerpted from a full profile, available here. To see Rienhoff’s TGF-β3 data, click here.